The Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome 2—Thrombolysis in Myocardial Infarction 51 [ATLAS ACS 2—TIMI 51] study was a Phase III trial of 15,526 patients. It evaluated 2 low doses of rivaroxaban, 2.5mg twice daily (n=5174) and 5mg twice daily (n=5176), compared with placebo as adjunctive therapy in post-ACS patients. It reported that the rivaoxaban doses, compared with placebo, reduced significantly the primary efficacy endpoint of cardiovascular death, myocardial infarction (MI), or stroke. This analysis of the study directly compared the two doses of rivaroxaban.
The study included patients aged 18 years or over with symptoms suggestive of ACS and diagnoses of ST-segment elevation MI, non-ST-segment elevation MI, or unstable angina. The baseline characteristics of the 2.5mg and 5mg twice daily treatment groups were similar.
The authors reported that there was no significant difference between rivaroxaban 2.5mg and 5mg twice daily of when assessing the primary endpoint (p=0.89). Also, there was no statistically significant differences between the two doses in the rates of MI (p=0.23) or stent thrombosis (p=0.59).
However, in the 2.5mg arm, 18 of 204 (8.8%) of the new MIs were fatal compared with 30 of 174 (17.2%) in the 5mg arm (p=0.074). The fraction of overall cardiac events that were fatal differed between the two treatment arms, with 82 of the 268 recurrent events (30.6%) being fatal in the 2.5mg arm compared with 112 (43.8%) of the 256 events in the 5mg arm (p=0.025). Total mortality was also significantly lower with the 2.5mg arm versus the 5mg arm (p=0.009).
Comparing the two active treatment arms in terms of safety, the rates of fatal bleeding with the 2.5mg arm were lower than with the 5mg treatment arm, with the hazard reaching a plateau over time (p=0.044). Rivaroxaban 2.5mg compared with 5mg twice daily resulted in significantly lower rates of bleeding requiring medical attention (12.9% vs. 16.2%, p<0.001).
The authors concluded that the addition of very low dose anticoagulation with rivaroxaban 2.5mg twice daily appeared to offer the more favourable option in patients with recent ACS.
NICE is in the process of developing guidance for rivaroxaban for the prevention of adverse outcomes in patients after the acute management of acute coronary syndrome. The technology appraisal is expected to be published in March 2015.